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Association of MHC Class II and PD-L1 Expression With Outcome in Classical Hodgkin Lymphoma

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Key Points

  • Higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells were associated with better progression-free survival.
  • MHC class II expression was associated with improved progression-free survival in patients receiving nivolumab > 12 months after myeloablative ASCT. 

As reported in the Journal of Clinical Oncology, Roemer et al found that programmed death cell ligand 1 (PD-L1) expression and major histocompatibility complex (MHC) class II positivity on Hodgkin Reed-Sternberg (HRS) cells may predict favorable outcome with programmed cell death protein 1 (PD-1) inhibitor treatment in classical Hodgkin lymphoma.

HRS cells are able to evade antitumor immunity through several mechanisms, including gains of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) and perturbed antigen presentation.

Study Details

In the study, HRS cells from archived tumor biopsies from patients with relapsed/refractory disease receiving nivolumab (Opdivo) in the CheckMate 205 trial were assessed for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD-L1 and the antigen presentation pathway components β2-microglobulin, MHC class I, and MHC class II by immunohistochemistry.

Associations With Outcome

There was a significant association between PD-L1 expression and magnitude of 9p24.1 copy number alterations in HRS cells (P = .001). Patients with tumors exhibiting higher-level 9p24.1 copy gain (P < .001) and increased PD-L1 expression (P = .026) had improved progression-free survival. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or progression-free survival (P = .07/ P = .38) with nivolumab therapy. HRS cell expression of MHC class II was predictive of complete remission (P = .03). MHC class II expression on HRS cells was not predictive of progression-free survival in patients who received nivolumab ≤ 12 months after myeloablative autologous stem-cell transplantation (ASCT), but was associated with prolonged progression-free survival among those treated > 12 months after ASCT (P = .014).

The investigators concluded, “Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In [classical Hodgkin lymphoma], clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.”

The study was funded by National Institutes of Health grants, Miller Family Fund, and Bristol-Myers Squibb.

Margaret A. Shipp, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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